EZH2 promotes metabolic reprogramming in glioblastomas through epigenetic repression of EAF2-HIF1α signaling.

EZH2 promotes metabolic reprogramming in glioblastomas through epigenetic repression of EAF2-HIF1α signaling.
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EZH2 通过 EAF2-HIF1 α 信号的表观遗传抑制促进胶质母细胞瘤中的代谢重编程

DOI:
10.18632/oncotarget.9761
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发表时间:
2016-07-19
期刊:
影响因子:
--
通讯作者:
Liu Q
Liu Q
中科院分区:
其他
文献类型:
--
作者:
Pang B;Zheng XR;Tian JX;Gao TH;Gu GY;Zhang R;Fu YB;Pang Q;Li XG;Liu Q

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癌细胞更喜欢糖酵解来进行能量代谢,即使有足够的氧气使其变得不必要。这被称为瓦尔堡效应,它促进肿瘤发生和恶性进展。在这项研究中,我们证明了EZH 2,一种参与肿瘤增殖,侵袭和转移的多方面致癌蛋白,通过激活瓦尔堡效应促进胶质母细胞瘤肿瘤发生和恶性进展。我们观察到HIF 1 α是EZH 2的靶点,其激活是EZH 2介导的代谢适应所必需的,并且HIF 1 α在EZH 2过表达时被激活。EZH 2抑制EAF 2的表达,EAF 2反过来上调HIF 1 α水平。我们从这些结果中得出结论,EZH 2部分通过EAF 2-HIF 1 α信号轴激活糖酵解来促进肿瘤发生和恶性进展。
Cancer cells prefer glycolysis for energy metabolism, even when there is sufficient oxygen to make it unnecessary. This is called the Warburg effect, and it promotes tumorigenesis and malignant progression. In this study, we demonstrated that EZH2, a multifaceted oncogenic protein involved in tumor proliferation, invasion and metastasis, promotes glioblastoma tumorigenesis and malignant progression through activation of the Warburg effect. We observed that HIF1α is a target of EZH2 whose activation is necessary for EZH2-mediated metabolic adaption, and that HIF1α is activated upon EZH2 overexpression. EZH2 suppressed expression of EAF2, which in turn upregulated HIF1α levels. We conclude from these results that EZH2 promotes tumorigenesis and malignant progression in part by activating glycolysis through an EAF2-HIF1α signaling axis.
Polycomb 在衰老过程中介导 INK4a/ARF 位点的表观遗传沉默和复制计时。
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